Discovery of dendronosesnoids A-T: novel structurally diverse sesquiterpenoids with antibacterial activity from...

Twenty novel sesquiterpenoids, dendronosesnoids A-T (1-20), including three copa-type (1-3), four cyclocopacamphane-type (4-7), and thirteen cadinane-type (8-20), were isolated from Dendrobium nobile. Their structures and absolute configurations were elucidated by spectroscopic analyses (HRESIMS, NMR, UV, and IR), combined with quantum chemical calculations and X-ray diffraction. Notably, compounds 1-3 feature an unusual caged tricyclo [5.3.0.0^3,8] decane skeleton reported for the first time from D. nobile. Compounds 4-7 are rare cyclocopacamphane sesquiterpenoids bearing a typical phenylpropyl moiety. Compounds 12-19 share a highly aromatized cadinane-type sesquiterpenoid scaffold, among which compounds 18 and 19 represent two new C₁₀ norsesquiterpenoids with a carbonyl group at C-10. Compound 19 displayed potent inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA) strains 171 and ATCC 12228, with a minimum inhibitory concentration (MIC) of 4 μg/mL for both. Notably, physiological analysis combined with electron microscopy observations indicated that the antibacterial activity of compound 19 is associated with the disruption of the bacterial cell membrane. These findings suggest that the sesquiterpenoids from D. nobile, especially dendronosesnoid S (19), hold great potential for the development of novel antibacterial agents.